Water → HCID 57707196, compound

Participants

Reaction Conditions

Reaction Steps

Methyl (3R)-6,6,6-trifluoro-3-(3-hydroxyphenyl)hexanoate or methyl (3S)-6,6,6-trifluoro-3-(3-hydroxyphenyl)hexanoate (68). A mixture of 3-hydroxyphenylboronic acid (available from Aldrich) (1.8 g, 13 mmol) and hydroxy[(S)-BINAP]-rhodium(I) dimer (0.19 g, 0.13 mmol) in 1,4-dioxane (10 mL, 2.5 mmol) was sparged with N2. To the mixture were added water (1.0 mL, 2.5 mmol) and (E)-ethyl 6,6,6-trifluorohex-2-enoate 68.B (0.56 mL, 2.5 mmol). The resulting red-brown solution was warmed to 45° C. and stirred for 3 hours (sealed vial). The mixture was cooled to room temperature, diluted with EtOAc, washed with saturated aqueous NaHCO3 and brine, dried (MgSO4), and concentrated. The residue was purified by silica gel flash chromatography (0-25% EtOAc/hexane) to afford (R)-ethyl 6,6,6-trifluoro-3-(3-hydroxyphenyl)hexanoate and (S)-ethyl 6,6,6-trifluoro-3-(3-hydroxyphenyl)hexanoate 68 as a pale yellow oil (84% e.e.). The enantiomerically enriched mixture was further purified by chiral HPLC (Chiralcel OD, 3% i-PrOH/hexane, 220 nm) to afford 68 as a colorless oil (0.65 g, >99% e.e.). The R enantiomer is believed to be the major product used in the following steps.

Provenance & Evidence